Anti-Siglec-15 antibody

Abstract

Provided is a pharmaceutical composition for treating and/or preventing abnormal bone metabolism targeting a protein encoded by a gene strongly expressed in osteoclasts. Specifically provided is a pharmaceutical composition containing an antibody which specifically recognizes human Siglec-15 and has an activity of inhibiting osteoclast formation, and the like.

The invention claimed is: 
     
       1. An antibody or antigen binding fragment thereof comprising:
 a light chain sequence that comprises a light chain variable region having CDRL1, CDRL2, and CDRL3, wherein CDRL1 comprises the amino acid sequence of SEQ ID NO: 47, CDRL2 comprises the amino acid sequence of SEQ ID NO: 48, and CDRL3 comprises the amino acid sequence of SEQ ID NO: 49, and a heavy chain sequence that comprises a heavy chain variable region having CDRH1, CDRH2, and CDRH3, wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 44, CDRH2 comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 45 and SEQ ID NO: 97, and CDRH3 comprises the amino acid sequence of SEQ ID NO: 46, wherein the antibody or antigen binding fragment thereof binds a Siglec-15 protein comprising the amino acid sequence of SEQ ID NO: 2 or 4, 
 wherein the light chain sequence is selected from the group consisting of: 
 (a) the light chain sequence comprises amino acid residues 21-238 of the amino acid sequence of SEQ ID NO: 69; 
 (b) the light chain sequence comprises amino acid residues 21-238 of the amino acid sequence of SEQ ID NO: 105; 
 (c) the light chain variable region comprises amino acid residues 21-133 of the amino acid sequence of SEQ ID NO: 69; and 
 (d) the light chain variable region comprises amino acid residues 21-133 of the amino acid sequence of SEQ ID NO: 105 
 or 
 wherein the heavy chain sequence is selected from the group consisting of: 
 (a) the heavy chain sequence comprises amino acid residues 20-466 of the amino acid sequence of SEQ ID NO: 101; 
 (b) the heavy chain sequence comprises amino acid residues 20-466 of the amino acid sequence of SEQ ID NO: 99; 
 (c) the heavy chain variable region comprises amino acid residues 20-140 of the amino acid sequence of SEQ ID NO: 101; and 
 (d) the heavy chain variable region comprises amino acid residues 20-140 of the amino acid sequence of SEQ ID NO: 99. 
 
     
     
       2. The antigen binding fragment of  claim 1 , selected from the group consisting of Fab, F(ab′)2, Fab′ and Fv. 
     
     
       3. The antibody or antigen binding fragment of  claim 1 , wherein the antigen binding fragment is an scFv. 
     
     
       4. The antibody or antigen binding fragment of  claim 1 , wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 45. 
     
     
       5. The antibody or antigen binding fragment of  claim 1 , wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 97. 
     
     
       6. A polynucleotide encoding the antibody or antigen binding fragment of  claim 1 . 
     
     
       7. A vector comprising the polynucleotide according to  claim 6 . 
     
     
       8. A transformed host cell comprising the polynucleotide according to  claim 6 . 
     
     
       9. A transformed host cell comprising the vector according to  claim 7 . 
     
     
       10. A method of producing an antibody comprising culturing the host cell according to  claim 8 , and purifying the antibody from the resulting culture product. 
     
     
       11. The antibody or antigen binding fragment of  claim 1 , wherein the light chain sequence comprises amino acid residues 21-238 of the amino acid sequence of SEQ ID NO: 69. 
     
     
       12. The antibody or antigen binding fragment of  claim 1 , wherein the heavy chain sequence comprises amino acid residues 20-466 of the amino acid sequence of SEQ ID NO: 101. 
     
     
       13. The antibody or antigen binding fragment of  claim 11 , wherein the heavy chain sequence comprises amino acid residues 20-466 of the amino acid sequence of SEQ ID NO: 101. 
     
     
       14. The antibody or antigen binding fragment of  claim 1 , wherein the light chain sequence comprises amino acid residues 21-238 of the amino acid sequence of SEQ ID NO: 105. 
     
     
       15. The antibody or antigen binding fragment of  claim 1 , wherein the heavy chain sequence comprises amino acid residues 20-466 of the amino acid sequence of SEQ ID NO: 99. 
     
     
       16. The antibody or antigen binding fragment of  claim 14 , wherein the heavy chain sequence comprises amino acid residues 20-466 of the amino acid sequence of SEQ ID NO: 99. 
     
     
       17. The antibody or antigen binding fragment of  claim 1 , wherein the light chain variable region comprises amino acid residues 21-133 of the amino acid sequence of SEQ ID NO: 69. 
     
     
       18. The antibody or antigen binding fragment of  claim 1 , wherein the heavy chain variable region comprises amino acid residues 20-140 of the amino acid sequence of SEQ ID NO: 101. 
     
     
       19. The antibody or antigen binding fragment of  claim 17 , wherein the heavy chain variable region comprises amino acid residues 20-140 of the amino acid sequence of SEQ ID NO: 101. 
     
     
       20. The antibody or antigen binding fragment of  claim 1 , wherein the light chain variable region comprises amino acid residues 21-133 of the amino acid sequence of SEQ ID NO: 105. 
     
     
       21. The antibody or antigen binding fragment of  claim 1 , wherein the heavy chain variable region comprises amino acid residues 20-140 of the amino acid sequence of SEQ ID NO: 99. 
     
     
       22. The antibody or antigen binding fragment of  claim 20 , wherein the heavy chain variable region comprises amino acid residues 20-140 of the amino acid sequence of SEQ ID NO: 99.